While many technologies for medical imaging are advanced, no simple and accurate imaging tool exists to guide early detection, tissue biopsy and optimal treatment for prostate cancer. More research and technology development are needed to explore reliable and quantitative imaging means for improved prostate cancer screening, diagnosis and prognosis. The overall hypothesis for this R01 proposal is that a novel Globally Convergent Method in combination with a transrectal, multi-channel optical imaging system can be developed and used in vivo for transrectal detection and diagnosis of prostate cancer in human. The Specific Aims are: Aim 1: develop and validate a globally convergent method (GCM) to obtain 2-dimentional (2- D) reconstructed images of optical parameters (both absorption and scattering parameters) that are characteristic of human prostate cancer. Aim 2: design, implement, and validate a transrectal, multi-channel optical imaging system that can be used to measure optical signals from human prostate glands for non-invasive or minimally invasive prostate cancer diagnosis or/and screen. Aim 3(a): experimentally validate the developed 2-D GCM using human prostate-like tissue phantoms so that appropriate refinement, modification, or calibration can be explored to improve both theoretical accuracy and experimental designs. Aim 3(b): perform optical imaging measurements on ex vivo human prostate glands, which are removed from patients during prostatectomy, and compare with histology results to validate the newly developed 2-D GCM. Aim 3(c): validate the 2-D GCM and transrectal imaging system by performing in vivo human prostate measurements during prostatectomy. The optical measurements will be carried out transrectally in the beginning of the surgery before the prostate is removed and then taken again on the same ex vivo prostate gland. Comparison between the in vivo and ex vivo results will be made and utilized for improvement of the 2-D GCM and transrectal imaging system. This proposed project is a feasibility study. We wish to show that the GCM is a direct and fast imaging reconstruction algorithm with proven mathematical foundation, leading to an economic and practical NIR imager for prostate cancer detection. Also, by combining the optical tomographic imaging technique with the novel design of transrectal optical probes, the research team has a unique opportunity to obtain optical and physiological signatures of prostate cancer in human, which will enable proper planning of a future trial with a statistically significant number of subjects. The long-term goal is to utilize optically derived signatures as finger-prints of prostate cancer to diagnose the cancer in the future. PUBLIC HEALTH RELEVANCE: While many technologies for medical imaging are advanced, there is no accurate imaging and diagnostic tool to guide early detection, tissue biopsy and optimal treatment for prostate cancer. More research and technology development are greatly needed for improved prostate cancer screening and prognosis. It would be highly desirable to develop a low-cost, quantitative, transrectal imaging system that allows routine, early, and accurate screen and detection for prostate cancer. The proposed project is a feasibility study to investigate a novel mathematical method that can be used along with a transrectal imaging system for early detection of prostate cancer. The developed mathematical tool will provide two-dimensional, tomographic images for human prostate cancer testing.